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Seizure Jul 2023The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS),... (Review)
Review
INTRODUCTION
The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.
METHODS
We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).
RESULTS
Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.
CONCLUSIONS
AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.
Topics: Humans; Down Syndrome; Epilepsy; Epilepsies, Myoclonic; Levetiracetam; Seizures; Alzheimer Disease; Electroencephalography; Anticonvulsants; Epilepsy, Generalized
PubMed: 37267668
DOI: 10.1016/j.seizure.2023.05.017 -
Neurology India 2010Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia,... (Review)
Review
Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects.
Topics: Cognition Disorders; Diagnostic Imaging; Electroencephalography; Humans; India; Muscle, Skeletal; Myoclonic Epilepsies, Progressive; Protein Tyrosine Phosphatases, Non-Receptor
PubMed: 20739785
DOI: 10.4103/0028-3886.68660 -
Epileptic Disorders : International... Oct 2023Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome characterized by the development of progressively worsening myoclonus, ataxia, and seizures. A molecular... (Review)
Review
Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome characterized by the development of progressively worsening myoclonus, ataxia, and seizures. A molecular diagnosis can now be established in approximately 80% of individuals with PME. Almost fifty genetic causes of PME have now been established, although some remain extremely rare. Herein, we provide a review of clinical phenotypes and genotypes of the more commonly encountered PMEs. Using an illustrative case example, we describe appropriate clinical investigation and therapeutic strategies to guide the management of this often relentlessly progressive and devastating epilepsy syndrome. This manuscript in the Genetic Literacy series maps to Learning Objective 1.2 of the ILAE Curriculum for Epileptology (Epileptic Disord. 2019;21:129).
Topics: Humans; Literacy; Myoclonic Epilepsies, Progressive; Unverricht-Lundborg Syndrome; Myoclonus; Ataxia
PubMed: 37616028
DOI: 10.1002/epd2.20152 -
Neurologia (Barcelona, Spain) Mar 2017Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated...
INTRODUCTION
Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges.
METHOD
We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed.
RESULTS
In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam.
CONCLUSIONS
The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.
Topics: Adult; Aged; Alzheimer Disease; Anticonvulsants; Down Syndrome; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Valproic Acid
PubMed: 25661268
DOI: 10.1016/j.nrl.2014.12.008 -
Clinical Dysmorphology Jan 2022Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM# 611726) is a rare autosomal recessive condition associated with pathogenic variants in... (Review)
Review
Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM# 611726) is a rare autosomal recessive condition associated with pathogenic variants in KCTD7, which encodes the BR-C,ttk and bab/pox virus and zinc finger domain-containing KCTD7 protein. We report four individuals from three Indian families presenting with an initial period of normal development, progressive myoclonic seizures followed by neuroregression and an abnormal electroencephalogram. We identified two novel missense variants, c.458G>C p.(Arg153Pro) and c.205C>G p.(Leu69Val) and one known disease-causing variant, c.280C>T p.(Arg94Trp) in KCTD7 by exome sequencing. We review the literature of 67 individuals with variants in KCTD7. Our study expands the molecular spectrum of KCTD7-related progressive myoclonic epilepsy.
Topics: Humans; Mutation, Missense; Myoclonic Epilepsies, Progressive; Potassium Channels; Exome Sequencing
PubMed: 34866617
DOI: 10.1097/MCD.0000000000000394 -
Paediatric Drugs Apr 2020The progressive myoclonic epilepsies (PMEs) represent a rare but devastating group of syndromes characterized by epileptic myoclonus, typically action-induced seizures,... (Review)
Review
The progressive myoclonic epilepsies (PMEs) represent a rare but devastating group of syndromes characterized by epileptic myoclonus, typically action-induced seizures, neurological regression, medically refractory epilepsy, and a variety of other signs and symptoms depending on the specific syndrome. Most of the PMEs begin in children who are developing as expected, with the onset of the disorder heralded by myoclonic and other seizure types. The conditions are considerably heterogenous, but medical intractability to epilepsy, particularly myoclonic seizures, is a core feature. With the increasing use of molecular genetic techniques, mutations and their abnormal protein products are being delineated, providing a basis for disease-based therapy. However, genetic and enzyme replacement or substrate removal are in the nascent stage, and the primary therapy is through antiepileptic drugs. Epilepsy in children with progressive myoclonic seizures is notoriously difficult to treat. The disorder is rare, so few double-blinded, placebo-controlled trials have been conducted in PME, and drugs are chosen based on small open-label trials or extrapolation of data from drug trials of other syndromes with myoclonic seizures. This review discusses the major PME syndromes and their neurogenetic basis, pathophysiological underpinning, electroencephalographic features, and currently available treatments.
Topics: Child; Humans; Myoclonic Epilepsies, Progressive; Research Design
PubMed: 31939107
DOI: 10.1007/s40272-019-00378-y -
Tremor and Other Hyperkinetic Movements... 2018Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterized by myoclonus, epilepsy, ataxia, and dementia. Diagnosis is... (Review)
Review
BACKGROUND
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterized by myoclonus, epilepsy, ataxia, and dementia. Diagnosis is challenging due to the heterogeneous presentation and symptomatic overlap with other spinocerebellar ataxias. Symptoms vary according to age of onset, with a mean age at onset of 31 years. A CAG repeat expansion in the gene results in neuronal intranuclear inclusions, variable neuronal loss, and astrocytosis in the globus pallidus, dentate and red nuclei. No disease-modifying or curative treatments are currently available.
METHODS
We performed an online literature search using PubMed for all articles published in an English Language format on the topics of DRPLA or over the last 10 years. Where these articles cited other research as support for findings, or statements, these articles were also reviewed. Contemporary articles from related research fields (e.g., Huntington's Disease) were also included to support statements.
RESULTS
Forty-seven articles were identified, 10 were unobtainable and 10 provided no relevant information. The remaining 27 articles were then used for the review template: seven case reports, seven case series, six model system articles (one review article), four population clinical and genetic studies (one review article), two general review articles, and one human gene expression study. Other cited articles or research from related fields gave a further 42 articles, producing a total of 69 articles cited: 15 case series (including eight family studies), 14 model systems (one review article), 14 population clinical and genetic studies (two review articles), 10 case reports, eight clinical trials/guidelines, four genetic methodology articles, three general review articles, and one human gene expression study.
DISCUSSION
DRPLA remains an intractable, progressive, neurodegenerative disorder without effective treatment. Early recognition of the disorder may improve patient understanding, and access to services and treatments. Large-scale studies are lacking, but are required to characterize the full allelic architecture of the disorder in all populations and the heterogeneous phenotypic spectrum, including neuroimaging findings, possible biomarkers, and responses to treatment.
Topics: Adult; Animals; Brain; Child; Disease Management; Disease Models, Animal; Female; Humans; Male; Myoclonic Epilepsies, Progressive; Nerve Tissue Proteins; Peptides; PubMed
PubMed: 30410817
DOI: 10.7916/D81N9HST -
Epilepsia 2001Epileptic encephalopathies are conditions in which neurologic deterioration results mainly from epileptic activity. It can be due to very frequent or severe seizures, or... (Review)
Review
Epileptic encephalopathies are conditions in which neurologic deterioration results mainly from epileptic activity. It can be due to very frequent or severe seizures, or to subcontinuous paroxysmal interictal activity. The former consists mainly of severe myoclonic epilepsy in infancy (SMEN), in which patients exhibit seizures from the middle of the first year of life with repeated episodes of status epilepticus, and migrating partial epilepsy in infancy, in which, from the first trimester of life, partial seizures affect various areas of the cortex randomly and in a subcontinuous fashion. Cases with subcontinuous paroxysmal interictal activity affect newborns with suppression bursts, thus consisting of either Ohtahara syndrome or neonatal myoclonic encephalopathy, and infants with infantile spasms (IS), although rare cases do not start until age 4 years. In childhood, it consists of various types of generalized seizures combined with either slow spike-waves of the Lennox-Gastaut syndrome (LGS) or with myoclonus and 3-Hz spike-waves of myoclonic-astatic epilepsy, and continuous spike-waves in slow sleep (CSWS) combined with various neuropsychological patterns including Landau-Kleffner syndrome, frontal lobe syndrome, orofacial dyspraxia, or negative myoclonus. Management differs for all these syndromes, with the combination of clobazam (CLB) and stiripentol (STP) being promising for SMEN, vigabatrin (VGB) for IS, lamotrigine (LTG) for LGS, and steroids for CSWS. It is important to avoid potential drug-induced worsening by phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), tiagabine (TGB), and VGB; in children and especially in infants, treatment with valproate is preferred each time the proper diagnosis is not reached.
Topics: Adolescent; Age Factors; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Brain Diseases; Child; Child, Preschool; Clobazam; Dioxolanes; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Infant, Newborn; Landau-Kleffner Syndrome; Spasms, Infantile; Treatment Outcome
PubMed: 11520318
DOI: 10.1046/j.1528-1157.2001.042suppl.3023.x -
Archives of Disease in Childhood Sep 1988The clinical and electroencephalographic features of 10 adolescents with juvenile myoclonic epilepsy are presented. The mean age on onset was 12.3 years. Myoclonic... (Review)
Review
The clinical and electroencephalographic features of 10 adolescents with juvenile myoclonic epilepsy are presented. The mean age on onset was 12.3 years. Myoclonic jerks, predominantly on awakening, occurred in all 10 and were associated with infrequent generalised tonic-clonic seizures in nine. Five had first degree relatives with seizures. The neurodevelopmental status was normal in eight and social integration good in seven. Waking interictal electroencephalograms showed normal background activity in nine, polyspike and wave in six, and single spike and wave in eight. Four were photosensitive. Failure to respond to other antiepileptic drugs was usual, but valproate monotherapy resulted in good or complete seizure control. Juvenile myoclonic epilepsy is a well defined clinical entity that responds well to valproate and is usually associated with a good outlook.
Topics: Adolescent; Adolescent Behavior; Anticonvulsants; Child; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Male; Social Behavior; Valproic Acid
PubMed: 3140737
DOI: 10.1136/adc.63.9.1049 -
Tremor and Other Hyperkinetic Movements... 2018Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical... (Review)
Review
BACKGROUND
Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.
METHODS
We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.
RESULTS
Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A "benign" phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.
DISCUSSION
Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.
Topics: Epilepsies, Myoclonic; Humans; Phenotype
PubMed: 29416935
DOI: 10.7916/D85155WJ